Home
JournalsCollections
For Authors For Reviewers For Editorial Board Members
Article Processing Charges Open Access
Ethics Advertising Policy
Editorial Policy Resource Center
Company Information Contact Us
Publications > Journals > Journal of Translational Gastroenterology > Article Full Text
Review Article
OPEN ACCESS

Download PDF

Impact of Helicobacter pylori Status on GERD, Barrett’s Esophagus and Esophageal Cancer

  • Xiang Liu,
  • Emily Weng and
  • Murali Dharan* 
Journal of Translational Gastroenterology   2023;1(2):87-93

doi: 10.14218/JTG.2023.00020

Received:

Revised:

Accepted:

Published online:

 Author information

Citation: Liu X, Weng E, Dharan M. Impact of Helicobacter pylori Status on GERD, Barrett’s Esophagus and Esophageal Cancer. J Transl Gastroen. 2023;1(2):87-93. doi: 10.14218/JTG.2023.00020.

Abstract

Helicobacter pylori (H. pylori) is an exceptionally common human pathogen infecting a large proportion of the world’s population. It is known to cause gastritis, peptic ulcer disease, non- cardiac gastric adenocarcinoma, and gastric mucosa-assisted lymphoid tissue lymphoma. Test and treat is a widely practiced strategy for H. pylori infection worldwide. While there are clear benefits of treating H. pylori infection, long-term adverse consequences of widespread eradication of this commonly identified pathogen remain an area of much debate. H. pylori infection affects gastric acid secretion and the relationships of the infection with gastroesophageal reflux disease (GERD), Barrett’s esophagus (BE), and esophageal adenocarcinoma (EAC) have been studied but remain controversial topics. Review of the most up-to-date evidence from studies performed in the last 20 years suggests a possible inverse relationship between the prevalence of H. pylori infection and GERD. A meta-analysis of a randomized controlled trial showed that eradication of the infection was more likely to cause increased incidence of GERD. Additionally, other studies have noted a significant protective effect of H. pylori infection, notably Cag A+ strains, against the development of BE and EAC. In this review article, we will discuss the impact of H. pylori infection status on GERD, BE, and esophageal cancer.

Keywords

H. pylori, Helicobacter pylori, Gastroesophageal reflux disease, Barrett’s esophagus, Esophageal adenocarcinoma, Esophageal cancer

Introduction

Helicobacter pylori (H. pylori) is a human pathogen that infects as many as 50% of the world’s population.1 It has been implicated in the etiology of gastritis, peptic ulcer disease, and noncardiac gastric adenocarcinoma and gastric mucosa-assisted lymphoid tissue-lymphoma. Given its carcinogenic potential, the current approach to H. pylori infection is to test and treat. Over the years, the relationship between H. pylori infection and acid reflux related diseases has been re-evaluated. It has been reported that eradication of H. pylori infection can lead to worsening symptomatic gastroesophageal reflux disease (GERD), particularly in patients with already weakened lower esophageal sphincter.2

GERD remains one of the most common diseases treated by gastroenterologists and primary care physicians. It is defined as the retrograde movement of gastric contents into the esophagus causing related symptoms and complications.3 Gastroesophageal reflux is considered part of normal physiology and can occur several times a day in a healthy patient without causing symptoms or mucosal injury.4 When the mechanism of luminal clearance and integrity of antireflux barriers are disrupted, pathologic GERD can occur due to prolonged gastric acid exposure to the esophageal mucosa. The most common and classic symptoms of GERD are heartburn and regurgitation, but it can also manifest as chest pain, hoarseness, or chronic cough.3 Mucosal injury can result in erosive esophagitis, peptic strictures, Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC).4 While GERD is common, up to 40 to 50 percent of patients with EAC do not experience classic GERD symptoms.3 Five-year survival of EAC after onset of symptoms remains poor at less than 20%.5

The prevalence of GERD and EAC has been increasing in the western hemisphere. While there is no proven causal relationship between H. pylori infection and GERD, the prevalence of H. pylori infection has been reported to be inversely related to GERD and EAC in earlier observational studies. However, the true effect of H. pylori infection on GERD and BE/EAC remains controversial.1,6,7 As we continue to treat H. pylori to reduce the incidence of gastric cancer and peptic ulcer disease, it is important to evaluate the impact of widespread eradication of H. pylori and its effect on gastroesophageal reflux related diseases. Recent American Journal of Gastroenterology guidelines have suggested a movement toward more noninvasive screening for BE/EAC without requiring GERD as a prerequisite symptom. Understanding all factors that may affect the incidence of GERD and BE/EAC will help targeted and optimal screening efforts to prevent EAC. This review examines the mechanism of how H. pylori affects reflux related diseases and the relationship between H. pylori infection and its eradication on the incidence of GERD, BE, and EAC.

Methods

A general literature search was conducted in Pubmed, EMBASE, Web of Science, and Google Scholar. Articles that discussed H. pylori, reflux disease, BE, and EAC were accessed. The following terms were used: (H. pylori) OR (Helicobacter pylori) AND ((esophageal cancer) OR (esophageal carcinoma) OR (esophageal adenocarcinoma) OR (Barrett’s esophagus) OR (GERD) OR (esophagitis) OR (acid reflux)).

Effect of H. pylori infection and the effect of H. pylori eradication on gastric acid secretion

Gastric acid secretion is thought to play a role in acid reflux disease, which can be affected by H. pylori infection in varying degrees based on its distribution in the stomach. Gastric antrum-predominant infection has been shown to increase the production of gastrin (by downregulating somatostatin secreted by antral D cells) leading to increase of acid production by parietal cells found in the gastric corpus.8H. pylori-induced corpus gastritis is associated with an inflammatory process that attenuates gastrin’s effect on parietal cells, resulting in an overall decrease in acid production, particularly in the setting of severe gastric atrophy.8

Eradication of antral-predominant H. pylori-associated gastritis may reduce gastrin levels and result in reduction of acid secretion. In those with severe corpus inflammation, eradication may increase acid secretion through removal of functional inhibition on parietal cells from inflammatory products.9 Such effects are thought secondary to upregulation of H+/K+-ATPase mRNA without a change in the number of parietal cells occurring at least after one to three months following H. pylori eradication.10,11 Data regarding long-term effects on acid secretion following eradication of H. pylori infection are lacking, but prolonged, severe corpus inflammation can lead to irreversible loss of parietal cells and achlorhydria.8 Thus, most studies have hypothesized that H. pylori infection contributes to the GERD-BE-EAC sequence through reduction in acid secretion, especially in the setting of atrophic gastritis.

Other postulated mechanisms on the effect of H. pylori on GERD, BE, and EAC

Kountouras et al.12 argued that the effect of acid secretion on the GERD-BE-EAC pathway was over emphasized. They proposed that H. pylori is involved in GERD pathophysiology through induction of inflammatory products such as prostaglandins which relaxes lower esophageal sphincter as well as gastrin induction leading to increased acid secretion that ultimately contributes to development of GERD. Gastrin may also be oncogenic and promotes esophageal carcinomatosis gastrin receptor expression in Barrett’s metaplasia specimens and promotion of metaplasia has been demonstrated in mice with hypergastrinemia.13H. pylori DNA refluxate in the esophagus might play a role in directly downregulating inflammatory response such as reducing cytokine production that is involved in acceleration of BE development.14 Association between insulin resistance and H. pylori infection has been reported with the dysmetabolic state likely promoting GERD-BE-EAC sequence although evidence is limited.15 High levels of leptin and ghrelin are associated with a higher risk of BE, and H. pylori infection may indirectly reduce levels of leptin and ghrelin.16,17 Ghrelin stimulates appetite and is associated with obesity, a major risk factor for development of GERD/BE/EAC. H. pylori may help maintain normal oral microbiota diversity. Alteration in the oral microbiome with increased gram-negative bacteria and decreased gram-positive bacterial profile has been associated with a higher risk of reflux esophagitis.18 Lastly, H. pylori-induced apoptosis of Barrett’s-derived EAC cells has also been reported.19

H. pylori and GERD

The development of reflux esophagitis after H. pylori eradication was first reported in 1995 by Schutze.20 Early epidemiological data suggested that decreasing prevalence of H. pylori infection in Western populations appeared to be associated with an increasing prevalence of GERD and EAC.21 Since then, there have been several studies suggesting potential increase in incidence of reflux disease after H. pylori eradication although such conclusion has remained controversial.22 Some studies have suggested that corpus gastritis may be protective for reflux disease. One Japanese study found that following H. pylori eradication, 33% of patients with corpus gastritis had reflux esophagitis compared to 13% in those without corpus gastritis.23 In North America, Vakil et al.24 conducted a randomized controlled trial in patients with nonnuclear dyspepsia and H. pylori infection. Antral-predominant H. pylori infection was noted in 55% of patients compared with corpus-predominant H. pylori infection, which was noted in only 6% of patients. The remainder had involvement at both sites. Symptoms of heartburn and regurgitation were found to be significantly improved after eradication in patients with antral-predominant gastritis. Esophagitis was more common in the eradication group but statistical significance was not reached.24 Another recent study done in Iran reported similar findings that GERD was more prevalent and significantly associated with antral gastritis.25 Such a pattern supports the mechanism that the effect of H. pylori on acid production may play a big role in the development of GERD. Antral gastritis is thought to be more common in the Western world, while corpus gastritis is more common in Asia; therefore, eradication of H. pylori would actually lead to less acid reflux disease in the Western world. While these studies may suggest possible regional variation in the pattern of H. pylori infection, larger studies are needed to help determine the true prevalence of antral or corpus-predominant H. pylori in different regions of the world.

Many other observational studies as well as several randomized controlled trials have also looked at the relationship between H. pylori status and incidence of GERD. We examined several meta-analyses on these studies performed in the last 20 years (Table 1). 26–33 In a meta-analysis of observational studies, H. pylori infection was associated with 26% decrease in GERD symptoms and a 30% reduction in erosive esophagitis.26H. pylori eradication is associated with increased incidence of GERD symptoms and erosive esophagitis, although statistical significance was not reached in the early meta-analyses of randomized controlled trial (RCT) and cohort studies as described in Table 1. Notably, most studies included in the analyses were North American and European studies. A subgroup analysis by Xie et al.27 showed that the incidence of GERD was especially increased in the Asian population after H. pylori eradication. A study by Mou et al.28 which included more Asian studies showed a significant increase in GERD incidence after eradication as well. However, their subgroup analysis did not show significant difference in either non-Asian or Asian studies. Of the seven meta-analyses of RCTs and cohort studies, three found significant increases in the incidence of GERD or erosive esophagitis after H. pylori eradication while the four other studies did not show significant difference.20,27,29–33 While it is unclear how the distribution of antral or corpus gastritis may have affected the outcome, the general trend seen in recent studies that included both Asian and Western populations suggests that H. pylori infection may be protective against GERD while its eradication may be associated with increased incidence of GERD and erosive esophagitis.

Table 1

Meta-analysis of H. pylori infection and the incidence of GERD/erosive esophagitis and the effect of H. pylori treatment on GERD/erosive esophagitis

ReferenceType of studies included in the meta-analysisOutcome: Incidence of GERD or Erosive esophagitis in H. pylori eradicated vs. persistent patients
Yaghoobi et al.,29 20107 RCTs, 5 cohort studiesErosive esophagitis OR = 1.11 (95% CI: 0.81–1.53, p = 0.52)
Symptomatic GERD OR =1.37 (95% CI: 0.89–2.12, p = 0.15)
Qian et al.,30 201111 RCTsErosive esophagitis OR = 0.97 (95% CI: 0.67–1.40; p = 0.88)
Symptomatic GERD OR = 0.88 (95% CI: 0.63–1.23, p = 0.46)
Saad et al.,31 201210 RCTsErosive esophagitis OR = 1.13 (95% CI: 0.72–1.78, p = 0.59)
Symptomatic GERD OR = 0.81 (95% CI: 0.56–1.17, p = 0.27)
Xie et al.,27 201343 Studies including, case–control, corhort, and RCTsSymptomatic GERD
Case-control (untreated patients) OR = 0.64 (95% CI: 0.49–0.83)
Cohort studies (eradicated patients) RR = 2.50 (95% CI: 1.46–4.26)
RCTs (eradicated patients) RR = 1.99 (95% CI: 1.23–3.22)
Tan et al.,32 201516 Cohort studiesSymptomatic GERD
OR = 0.87 (95% CI: 0.66–1.14, p = 0.103)
Mou et al.,28 202019 RTCsSymptomatic GERD
RR = 1.54 (95% CI: 1.06–2.24, p = 0.02)
Zhao et al.,33 202017 RCTsErosive esophagitis OR = 1.67 (95% CI: 1.12–2.48, p = 0.01)
Symptomatic GERD OR = 1.04 (95% CI: 0.84–1.29, p = 0.71)
Zamani et al.,26 202136 Cross- sectional and case-control studies7 Cross–sectional studies
Prevalence of H. pylori infection and incidence of symptomatic GERD
OR = 0.74 (95% CI: 0.61–0.90)
26 Cross–sectional studies
Prevalence of H. pylori infection and incidence of erosive esophagitis OR = 0.70 (95% CI: 0.58–0.84)
4 Case-controlled studies
Prevalence of H. pylori infection and incidence of symptomatic GERD OR = 1.10 (95% CI: 0.85–0.143)

CI, confidence interval; GERD, gastroesophageal reflux disease; OR, odds ratio; RCT, randomized controlled trial; RR, relative risk.

From a mechanistic point of view, H.pylori infection has not been shown to directly impact the competency of the esophago-gastric junction or esophageal peristalsis.34 It is also not known whether colonization of esophageal mucosa by H.pylori affects mucosal sensitivity to acid exposure. It is likely that the primary effect of H.pylori infection on GERD is to modify the nature of the refluxate from the stomach and this may be different in antral-predominant vs. corpus-predominant infection. Another possible explanation is that gastric bicarbonate levels are restored to baseline after H.pylori eradication without significant change in acid production.

H. pylori and BE

BE occurs when the esophageal squamous epithelium is replaced by specialized columnar epithelium with goblet cells causing intestinal metaplasia in the distal esophagus.35 Increasing BE segment length is associated with an increased risk of progression to EAC.36 Short-segment BE (<3 cm) and long-segment BE (≥3 cm) carry risks of progression to EAC of 0.07%, and 0.25%, respectively.37 BE is closely associated with GERD and is the only known precursor to EAC with increasing incidence in both North America and Europe.38 BE is detected in 10–15% of patients with GERD.39 Given its association with GERD, it would be reasonable to expect that H. pylori infection would be protective against BE. However, early data did not reveal a clear trend and studies have shown mixed effects of H. pylori infection on incidence of BE.40–42

Table 2 summarizes five meta-analyses of observational studies evaluating the association between H. pylori infection and BE.43–47 Wang et al showed no significant difference in the overall prevalence of H. pylori infection in BE and healthy controls.43 Subgroup analysis favored a lower prevalence of H. pylori infection in BE patients. Fischbach et al.44 included 49 observational studies but after accounting for bias and correct measurement of H. pylori infection, only four studies were found acceptable and showed an overall protective effect. A similar result was noted when considering only the USA studies. Subgroup analysis of CagA positivity in seven studies showed a protective effect against BE. An analysis by Eross et al.45 that included 72 studies also showed that H. pylori infection protected against BE. The protective effect was more pronounced in dysplastic BE and for long-segment BE. Their CagA positivity analysis included four additional studies to Fischbach’s analysis and found a significant protective effect. A similar association was found in two other recent studies.46,47 While earlier studies found an inconclusive association between H. pylori infection and BE, recent meta-analyses have all reported significant protective effects of H. pylori, especially against dysplastic and long-segment disease, which carry a higher potential to progress to EAC. Notably, these studies reported a high level of heterogeneity and many studies used serology as a marker for H. pylori positivity.

Table 2

Meta-analysis of observational studies comparing the prevalence of H. pylori infection in patients with or without BE

ReferenceType of studies included in the meta-analysisOutcome: Prevalence of H. pylori infection in patients with or without BE
Wang et al.,43 200912 Case-control studies42.9% vs. 43.9%, OR = 0.74 (95% CI: 0.40–1.37, p = 0.34)
Subgroup analysis:
23.1% vs. 42.7%, OR = 0.50 (95% CI: 0.27–0.93, p = 0.03)
Fischbach et al.,44 201249 Observation studies4 Studies included after accounting for bias
RR = 0.46 (95% CI: 0.35–0.60)
10 USA studies
RR = 0.46 (95% CI: 0.40–0.53)
7 studies with CagA-positive infection
RR = 0.38 (95% CI: 0.19–0.78)
Eross et al.,45 201872 Observational studiesOR = 0.68 (95% CI: 0.58–0.79, p < 0.001).
Dysplastic BE
OR = 0.37 (95% CI: 0.26–0.51, p < 0.001)
Long-segment BE
OR = 0.25 (95% CI: 0.11–0.59, p = 0.001)
Du et al.,46 202146 Observational studiesOR = 0.70 (95% CI: 0.51–0.96, p = 0.03)
CagA-positive H. pylori infection
OR = 0.28 (95% CI: 0.15–0.54, p = 0.0002)
Long-segment BE
OR = 0.47 (95% CI: 0.25–0.90; p = 0.02)
Ma et al.,47 202224 Observational studiesOR = 0.53 (95% CI: 0.45–0.64; p < 0.001)
CagA–positive H. pylori infection
OR = 0.25 (95% CI: 0.15–0.44, p = 0.000)
Long-segment BE
OR = 0.39 (95% CI: 0.18–0.86, p = 0.019)

BE, Barrett’s esophagus; CI, confidence interval; OR, odds ratio; RCT, randomized controlled trial; RR, relative risk.

H. pylori and EAC

EAC has been the most common esophageal cancer in the USA since the 1970s and has shown increasing prevalence in the western hemisphere.48 This appears to coincide with an increased rate of eradication of H. pylori which has been linked to a possible protective effect against EAC in early epidemiologic studies.49 EAC has a very low 5-year survival rate; therefore, it is important to identify predisposing factors to help mitigate the risks of developing EAC. The five most recent meta-analysis that were identified are shown in Table 3.48,50-53 Rokkas et al.50 showed that H. pylori infection was less frequently identified in patients with EAC. CagA-positive infection was also significantly lower in patients with EAC. A meta-analysis by Zhuo et al.51 reported similar findings. Three subsequent studies also agreed with the findings that suggested H. pylori infections are less commonly found in patients with EAC.48,52,53 All these meta-analyses support an association between H. pylori infection and EAC, with the bacteria exerting a possible protective effect, especially strains that are CagA-positive.

Table 3

Meta-analysis of observational studies comparing the prevalence of H. pylori infection in patients with or without EAC or ESCC

ReferenceType of studies included in the meta-analysisOutcome: Prevalence of H. pylori infection in patients with or without esophageal cancer (EAC or ESCC)
Rokkas et al.,50 200718 Observational studiesEAC (10 studies)
OR = 52 (95% CI: 0.37–0.73, p < 0.001)
CagA-positive H. pylori infection (6 studies)
OR = 0.51 (95% CI: 0.31– 0.82, p < 0.006)
ESCC (5 studies)
OR = 0.86 (95% CI: 0.56–1.33, p < 0.48)
Zhuo et al.,51 200812 Case-control studiesEAC (9 studies)
OR = 0.58 (95% CI: 0.48–0.70, p < 0.01)
ESCC (5 studies)
OR = 0.80 (95% CI: 0.45–1.43, p < 0.05)
Islami et al.,52 200819 Observational studiesEAC (13 studies)
OR = 0.56 (95% CI: 0.46–0.68)
CagA-positive H. pylori infection (5 studies)
OR = 0.41 (95% CI: 0.28–0.62)
ESCC (9 studies)
OR = 1.10 (95% CI: 0.78–1.55)
Xie et al.,53 201319 Observational studiesEAC (15 studies)
OR = 0.59 (95% CI: 0.51–0.68)
EAC CagA-positive H. pylori infection (8 studies)
OR = 0.56 (95% CI: 0.45–0.70)
ESCC (16 studies)
OR = 0.97 (95% CI: 0.76–1.24)
Asian studies only
OR = 0.66 (95% CI: 0.43–0.89)
ESCC CagA-positive H. pylori infection (9 studies)
OR = 0.77 (95% CI: 0.65–0.92)
Nie et al.,48 201428 Observational studiesEAC (13 studies)
OR = 0.57 (95% CI: 0.44–0.73)
EAC CagA-positive H. pylori infection (8 studies)
OR = 0.64 (95% CI: 0.52–0.79)
ESCC (19 studies)
OR = 1.16 (95% CI: 0.83–1.60)
ESCC CagA-positive H. pylori infection (7 studies)
OR = 0.97 (95% CI: 0.79–1.19).
ESCC CagA-positive H. pylori infection with stratified analysis
Asian studies
OR = 74 (95% CI: 0.57–0.97)
non-Asian studies
OR = 1.41 (95% CI: 1.02–1.94)

CI, confidence interval; EAC, esophageal adenocarcinoma; ESCC, esophageal squamous cell carcinoma; OR, odds ratio; RCT, randomized controlled trial; RR, relative risk.

H. pylori and esophageal squamous cell carcinoma (ESCC)

While ESCC is more common in Asian countries and not associated with GERD, studies have looked at its association with H. pylori as well. As shown in Table 3, Most studies did not find a significant relationship between ESCC and H. pylori. Two meta-analysis found a possible protective effect of CagA-positive infection against ESCC in Asian studies, but the opposite was found in non-Asian studies.48,53

Conclusions

Evidence from recent studies mostly shows a significant inverse correlation between H. pylori infection and GERD, BE, and EAC. Studies of the effect of H. pylori eradication on the incidence of GERD have reported more heterogeneous results. The majority of observational data support the notion that H. pylori infection protects against the development of BE and EAC. Infection with CagA-positive H. pylori strains also appears to confer significant protection. Although these meta-analyses included many of the same individual studies, they still showed a consistent inverse relationship between H. pylori infection and GERD-related diseases. While there is more evidence from randomized controlled trials on the effect of H. pylori infection on GERD, more prospective cohort studies regarding the effect of H. pylori infection on BE and EAC are needed.

However, the trend noted in these meta-analyses is not exactly consistent with what was previously observed in the Western world where H. pylori infections were thought to be antrum-predominant, and GERD was expected to improve after the eradication of antrum-predominant H. pylori infection following reversal of hypergastrinemia and the consequent reduction in acid secretion. Perhaps this explains the heterogeneity of the results seen in meta-analysis on GERD that included both Asian and Western studies. It also suggests that H. pylori may have a different degree of impact on each stage of the GERD-BE-EAC sequence as acid secretion is likely not the sole mechanism involved. Its involvement in downregulating tumor-promoting inflammatory response and maintaining oral microbiota balance as well as its interaction with esophageal epithelial cells likely play a role, although more studies are needed to better understand the pathogenesis. A possible inverse relationship between CagA positivity and EAC/ESCC is an interesting observation with unclear mechanism.

Treatment of H. pylori is widely adopted in clinical practice to prevent complications such as atrophic gastritis, peptic ulcer disease, and gastric cancer; therefore, it is not appropriate to withhold H. pylori treatment to prevent GERD and related complications. While there is no strong evidence that H. pylori eradication causes or predisposes to GERD, it may likely unmask pre-existing GERD. However, management of H. pylori infected patients at increased risk for GERD or EAC may warrant an individualized approach. With large portions of the Western population developing EAC without having significant GERD symptoms, it is important to identify additional risk factors that increase the risks of EAC. As a different strategy is employed to increase screening for EAC in the absence of chronic GERD, understanding whether H. pylori increases the risk of BE/EAC is important to determine if it should be considered as an additional risk factor to be included in the algorithm for EAC screening. More research is needed in this subset of patients to delineate the best management strategy.

Abbreviations

BE: 

Barrett’s esophagus

CI: 

confidence interval

EAC: 

esophageal adenocarcinoma

ESCC: 

esophageal squamous cell carcinoma

GERD: 

gastroesophageal reflux disease

OR: 

odds ratio

RCT: 

randomized controlled trial

RR: 

relative risk

Declarations

Acknowledgement

None.

Funding

None.

Conflict of interest

The authors have no conflict of interests related to this publication.

Authors’ contributions

Contributed to study concept and design (XL, EW, MD), acquisition of data (XL, EW), data analysis (XL, EW), drafting of the manuscript (XL, EW), critical revision of the manuscript (XL, EW, MD), and supervision of the project and final approval (MD).

References

  1. Chey WD, Leontiadis GI, Howden CW, Moss SF. ACG Clinical Guideline: Treatment of Helicobacter pylori Infection. Am J Gastroenterol 2017;112(2):212-239 View Article PubMed/NCBI
  2. Fukuchi T, Ashida K, Yamashita H, Kiyota N, Tsukamoto R, Takahashi H, et al. Influence of cure of Helicobacter pylori infection on gastric acidity and gastroesophageal reflux: study by 24-h pH monitoring in patients with gastric or duodenal ulcer. J Gastroenterol 2005;40(4):350-360 View Article PubMed/NCBI
  3. Katz PO, Dunbar KB, Schnoll-Sussman FH, Greer KB, Yadlapati R, Spechler SJ. ACG Clinical Guideline for the Diagnosis and Management of Gastroesophageal Reflux Disease. Am J Gastroenterol 2022;117(1):27-56 View Article PubMed/NCBI
  4. Feldman M, Friedman LS, Brandt LJ. Sleisenger and Fordtran’s Gastrointestinal and Liver Disease, 11th ed. Elsevier; 2020 View Article PubMed/NCBI
  5. Codipilly DC, Sawas T, Dhaliwal L, Johnson ML, Lansing R, Wang KK, et al. Epidemiology and Outcomes of Young-Onset Esophageal Adenocarcinoma: An Analysis from a Population-Based Database. Cancer Epidemiol Biomarkers Prev 2021;30(1):142-149 View Article PubMed/NCBI
  6. Hong SJ, Kim SW. Helicobacter pylori Infection in Gastroesophageal Reflux Disease in the Asian Countries. Gastroenterol Res Pract 2015;2015:985249 View Article PubMed/NCBI
  7. Gatenby P, Soon Y. Barrett’s oesophagus: Evidence from the current meta-analyses. World J Gastrointest Pathophysiol 2014;5(3):178-187 View Article PubMed/NCBI
  8. El-Omar EM. Mechanisms of increased acid secretion after eradication of Helicobacter pylori infection. Gut 2006;55(2):144-146 View Article PubMed/NCBI
  9. El-Omar EM, Oien K, El-Nujumi A, Gillen D, Wirz A, Dahill S, et al. Helicobacter pylori infection and chronic gastric acid hyposecretion. Gastroenterology 1997;113(1):15-24 View Article PubMed/NCBI
  10. Osawa H, Kita H, Ohnishi H, Hoshino H, Mutoh H, Ishino Y, et al. Helicobacter pylori eradication induces marked increase in H+/K+-adenosine triphosphatase expression without altering parietal cell number in human gastric mucosa. Gut 2006;55(2):152-157 View Article PubMed/NCBI
  11. Furuta T, Baba S, Takashima M, Shirai N, Xiao F, Futami H, et al. H+/K+-adenosine triphosphatase mRNA in gastric fundic gland mucosa in patients infected with Helicobacter pylori. Scand J Gastroenterol 1999;34(4):384-390 View Article PubMed/NCBI
  12. Polyzos SA, Zeglinas C, Artemaki F, Doulberis M, Kazakos E, Katsinelos P, et al. Helicobacter pylori infection and esophageal adenocarcinoma: a review and a personal view. Ann Gastroenterol 2018;31(1):8-13 View Article PubMed/NCBI
  13. Lee Y, Urbanska AM, Hayakawa Y, Wang H, Au AS, Luna AM, et al. Gastrin stimulates a cholecystokinin-2-receptor-expressing cardia progenitor cell and promotes progression of Barrett’s-like esophagus. Oncotarget 2017;8(1):203-214 View Article PubMed/NCBI
  14. Luther J, Owyang SY, Takeuchi T, Cole TS, Zhang M, Liu M, et al. Helicobacter pylori DNA decreases pro-inflammatory cytokine production by dendritic cells and attenuates dextran sodium sulphate-induced colitis. Gut 2011;60(11):1479-1486 View Article PubMed/NCBI
  15. Polyzos SA, Kountouras J, Zavos C, Deretzi G. The association between Helicobacter pylori infection and insulin resistance: a systematic review. Helicobacter 2011;16(2):79-88 View Article PubMed/NCBI
  16. Francois F, Roper J, Goodman AJ, Pei Z, Ghumman M, Mourad M, et al. The association of gastric leptin with oesophageal inflammation and metaplasia. Gut 2008;57(1):16-24 View Article PubMed/NCBI
  17. Nwokolo CU, Freshwater DA, O’Hare P, Randeva HS. Plasma ghrelin following cure of Helicobacter pylori. Gut 2003;52(5):637-640 View Article PubMed/NCBI
  18. Liang T, Liu F, Liu L, Zhang Z, Dong W, Bai S, et al. Effects of Helicobacter pylori Infection on the Oral Microbiota of Reflux Esophagitis Patients. Front Cell Infect Microbiol 2021;11:732613 View Article PubMed/NCBI
  19. Jones AD, Bacon KD, Jobe BA, Sheppard BC, Deveney CW, Rutten MJ. Helicobacter pylori induces apoptosis in Barrett’s-derived esophageal adenocarcinoma cells. J Gastrointest Surg 2003;7(1):68-76 View Article PubMed/NCBI
  20. Schütze K, Hentschel E, Dragosics B, Hirschl AM. Helicobacter pylori reinfection with identical organisms: transmission by the patients’ spouses. Gut 1995;36(6):831-833 View Article PubMed/NCBI
  21. el-Serag HB, Sonnenberg A. Opposing time trends of peptic ulcer and reflux disease. Gut 1998;43(3):327-333 View Article PubMed/NCBI
  22. Nakajima S, Hattori T. Oesophageal adenocarcinoma or gastric cancer with or without eradication of Helicobacter pylori infection in chronic atrophic gastritis patients: a hypothetical opinion from a systematic review. Aliment Pharmacol Ther 2004;20(Suppl 1):54-61 View Article PubMed/NCBI
  23. Hamada H, Haruma K, Mihara M, Kamada T, Yoshihara M, Sumii K, et al. High incidence of reflux oesophagitis after eradication therapy for Helicobacter pylori: impacts of hiatal hernia and corpus gastritis. Aliment Pharmacol Ther 2000;14(6):729-735 View Article PubMed/NCBI
  24. Vakil N, Talley NJ, Stolte M, Sundin M, Junghard O, Bolling-Sternevald E. Patterns of gastritis and the effect of eradicating Helicobacter pylori on gastro-oesophageal reflux disease in Western patients with non-ulcer dyspepsia. Aliment Pharmacol Ther 2006;24(1):55-63 View Article PubMed/NCBI
  25. Nobakht H, Boghratian A, Sohrabi M, Panahian M, Rakhshani N, Nikkhah M, et al. Association between Pattern of Gastritis and Gastroesophageal Reflux Disease in Patients with Helicobacter Pylori Infection. Middle East J Dig Dis 2016;8(3):206-211 View Article PubMed/NCBI
  26. Zamani M, Alizadeh-Tabari S, Hasanpour AH, Eusebi LH, Ford AC. Systematic review with meta-analysis: association of Helicobacter pylori infection with gastro-oesophageal reflux and its complications. Aliment Pharmacol Ther 2021;54(8):988-998 View Article PubMed/NCBI
  27. Xie T, Cui X, Zheng H, Chen D, He L, Jiang B. Meta-analysis: eradication of Helicobacter pylori infection is associated with the development of endoscopic gastroesophageal reflux disease. Eur J Gastroenterol Hepatol 2013;25(10):1195-1205 View Article PubMed/NCBI
  28. Mou WL, Feng MY, Hu LH. Eradication of Helicobacter Pylori Infections and GERD: A systematic review and meta-analysis. Turk J Gastroenterol 2020;31(12):853-859 View Article PubMed/NCBI
  29. Yaghoobi M, Farrokhyar F, Yuan Y, Hunt RH. Is there an increased risk of GERD after Helicobacter pylori eradication?: a meta-analysis. Am J Gastroenterol 2010;105(5):1007-1013 View Article PubMed/NCBI
  30. Qian B, Ma S, Shang L, Qian J, Zhang G. Effects of Helicobacter pylori eradication on gastroesophageal reflux disease. Helicobacter 2011;16(4):255-265 View Article PubMed/NCBI
  31. Saad AM, Choudhary A, Bechtold ML. Effect of Helicobacter pylori treatment on gastroesophageal reflux disease (GERD): meta-analysis of randomized controlled trials. Scand J Gastroenterol 2012;47(2):129-135 View Article PubMed/NCBI
  32. Tan J, Wang Y, Sun X, Cui W, Ge J, Lin L. The effect of Helicobacter pylori eradication therapy on the development of gastroesophageal reflux disease. Am J Med Sci 2015;349(4):364-371 View Article PubMed/NCBI
  33. Zhao Y, Li Y, Hu J, Wang X, Ren M, Lu G, et al. The Effect of Helicobacter pylori Eradication in Patients with Gastroesophageal Reflux Disease: A Meta-Analysis of Randomized Controlled Studies. Dig Dis 2020;38(4):261-268 View Article PubMed/NCBI
  34. Shirota T, Kusano M, Kawamura O, Horikoshi T, Mori M, Sekiguchi T. Helicobacter pylori infection correlates with severity of reflux esophagitis: with manometry findings. J Gastroenterol 1999;34(5):553-559 View Article PubMed/NCBI
  35. Shaheen NJ, Falk GW, Iyer PG, Souza RF, Yadlapati RH, Sauer BG, et al. Diagnosis and Management of Barrett’s Esophagus: An Updated ACG Guideline. Am J Gastroenterol 2022;117(4):559-587 View Article PubMed/NCBI
  36. Krishnamoorthi R, Singh S, Ragunathan K, Visrodia K, Wang KK, Katzka DA, et al. Factors Associated With Progression of Barrett’s Esophagus: A Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol 2018;16(7):1046-1055.e8 View Article PubMed/NCBI
  37. Hamade N, Vennelaganti S, Parasa S, Vennalaganti P, Gaddam S, Spaander MCW, et al. Lower Annual Rate of Progression of Short-Segment vs Long-Segment Barrett’s Esophagus to Esophageal Adenocarcinoma. Clin Gastroenterol Hepatol 2019;17(5):864-868 View Article PubMed/NCBI
  38. Cook MB, Thrift AP. Epidemiology of Barrett’s Esophagus and Esophageal Adenocarcinoma: Implications for Screening and Surveillance. Gastrointest Endosc Clin N Am 2021;31(1):1-26 View Article PubMed/NCBI
  39. Shaheen NJ, Falk GW, Iyer PG, Gerson LB, American College of Gastroenterology. View Article PubMed/NCBI
  40. Csendes A, Smok G, Cerda G, Burdiles P, Mazza D, Csendes P. Prevalence of Helicobacter pylori infection in 190 control subjects and in 236 patients with gastroesophageal reflux, erosive esophagitis or Barrett’s esophagus. Dis Esophagus 1997;10(1):38-42 View Article PubMed/NCBI
  41. Henihan RD, Stuart RC, Nolan N, Gorey TF, Hennessy TP, O’Morain CA. Barrett’s esophagus and the presence of Helicobacter pylori. Am J Gastroenterol 1998;93(4):542-546 View Article PubMed/NCBI
  42. Corley DA, Kubo A, Levin TR, Block G, Habel L, Zhao W, et al. Helicobacter pylori infection and the risk of Barrett’s oesophagus: a community-based study. Gut 2008;57(6):727-733 View Article PubMed/NCBI
  43. Wang C, Yuan Y, Hunt RH. Helicobacter pylori infection and Barrett’s esophagus: a systematic review and meta-analysis. Am J Gastroenterol 2009;104(2):492-500 View Article PubMed/NCBI
  44. Fischbach LA, Nordenstedt H, Kramer JR, Gandhi S, Dick-Onuoha S, Lewis A, et al. The association between Barrett’s esophagus and Helicobacter pylori infection: a meta-analysis. Helicobacter 2012;17(3):163-175 View Article PubMed/NCBI
  45. Erőss B, Farkas N, Vincze Á, Tinusz B, Szapáry L, Garami A, et al. Helicobacter pylori infection reduces the risk of Barrett’s esophagus: A meta-analysis and systematic review. Helicobacter 2018;23(4):e12504 View Article PubMed/NCBI
  46. Du YL, Duan RQ, Duan LP. Helicobacter pylori infection is associated with reduced risk of Barrett’s esophagus: a meta-analysis and systematic review. BMC Gastroenterol 2021;21(1):459 View Article PubMed/NCBI
  47. Ma S, Guo X, Wang C, Yin Y, Xu G, Chen H, et al. Association of Barrett’s esophagus with Helicobacter pylori infection: a meta-analysis. Ther Adv Chronic Dis 2022;13:20406223221117971 View Article PubMed/NCBI
  48. Nie S, Chen T, Yang X, Huai P, Lu M. Association of Helicobacter pylori infection with esophageal adenocarcinoma and squamous cell carcinoma: a meta-analysis. Dis Esophagus 2014;27(7):645-653 View Article PubMed/NCBI
  49. Chow WH, Blaser MJ, Blot WJ, Gammon MD, Vaughan TL, Risch HA, et al. An inverse relation between cagA+ strains of Helicobacter pylori infection and risk of esophageal and gastric cardia adenocarcinoma. Cancer Res 1998;58(4):588-590 View Article PubMed/NCBI
  50. Rokkas T, Pistiolas D, Sechopoulos P, Robotis I, Margantinis G. Relationship between Helicobacter pylori infection and esophageal neoplasia: a meta-analysis. Clin Gastroenterol Hepatol 2007;5(12):1413-1417.E2 View Article PubMed/NCBI
  51. Zhuo X, Zhang Y, Wang Y, Zhuo W, Zhu Y, Zhang X. Helicobacter pylori infection and oesophageal cancer risk: association studies via evidence-based meta-analyses. Clin Oncol (R Coll Radiol) 2008;20(10):757-762 View Article PubMed/NCBI
  52. Islami F, Kamangar F. Helicobacter pylori and esophageal cancer risk: a meta-analysis. Cancer Prev Res (Phila) 2008;1(5):329-338 View Article PubMed/NCBI
  53. Xie FJ, Zhang YP, Zheng QQ, Jin HC, Wang FL, Chen M, et al. Helicobacter pylori infection and esophageal cancer risk: an updated meta-analysis. World J Gastroenterol 2013;19(36):6098-6107 View Article PubMed/NCBI

Copyright © 2023 Authors. This is an Open Access article distributed under the terms of the Creative Commons Attribution-Noncommercial 4.0 License (CC BY-NC 4.0), permitting all non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

  • © 2024 Xia & He Publishing Inc.
  • Total visits : 2187308
  • Visits today : 2158